Allograft rejection and tumor immunity are generally considered to be manifestations of cell-mediated immune mechanisms of which cytotoxic T lymphocytes (CTL) are of major importance. Lymphoid cells are able to generate two kinds of CTL: allogeneic and major histocompatibility complex (MHC) restricted, hapten specific (syngeneic). Whereas allogeneic CTL are thought to be important in allograft rejection, syngeneic CTL are thought to be of importance in surveillance against autologous neoplastic cells and against infections. This project will compare the mechanisms of generation of allogeneic versus syngeneic trinitrophenyl (TNP)-CTL, placing the comparisons on a quantitative footing whenever possible. We have established so far that the soluble lymphokines, interleukin 1 (Il-1) and interleukin 2 (Il-2), are not detectable in the supernatants of syngeneic mixed lymphocyte culture (MLC), while they are easily demonstrable in the supernatants of allogeneic MLC. It appears that the supernatants of syngeneic MLC contain a helper factor distinct from either Il-1 or Il-2. The functional as well as the physicochemical properties of this lymphokine will be examined. Additionally, I have reported that Il-2-containing preparations, upon incubation with normal lymphocytes and in the absence of any added antigen, lead to the generation of CTL capable of lysing TNP-modified syngeneic lymphoid target cells as well as unmodified autologous tumors. This finding will be expanded by determining the spectrum of susceptible target cells and by determining the frequency of the CTL precursors by limiting dilution analysis. The exact lymphokine involved will be determined by sequential chromatographic purification of the Il-2-containing preparations. Upon establishing the lymphokine(s) involved and upon obtaining this lymphokine(s) in pure form, experiments will be done in vivo in a murine model to examine the ability of such lymphokines to induce tumor regression. (LB)